Clozapine Withdrawal-Induced Malignant Catatonia or Neuroleptic Malignant Syndrome: A Case Report and a Brief Review of the Literature

Belteczki, Zsuzsanna; Ujvari, Julia; Döme, Péter

doi:10.1097/wnf.0000000000000462

Cited by 15 publications

(7 citation statements)

References 55 publications

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“…The onset of withdrawal catatonia is 3-7 d after discontinuation, and the duration is 3-10 d. Also, it appears to present without electroencephalography abnormalities, such as diffuse slowing[ 128 ]. Moreover, there are sporadic reports of withdrawal catatonia secondary to antipsychotics and other psychotropics, such as clozapine[ 131 ], olanzapine[ 94 ], risperidone and olanzapine and chlorpromazine[ 56 ], haloperidol and cyamemazine[ 132 ], bromperidol and levomepromazine[ 133 ], amantadine[ 79 ], gabapentin[ 64 , 134 ], and lithium[ 94 ].…”

Section: Resultsmentioning

confidence: 99%

Catatonia in older adults: A systematic review

Jaimes-Albornoz¹,

Pellon-Santamaria²,

Nizama-Vía³

et al. 2022

WJP

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BACKGROUND Catatonia is a complex psychomotor syndrome that often goes unrecognized and untreated, even though its classification has evolved in recent years. Prompt and correct identification of catatonia allows for highly effective treatment and prevention of possible complications. The underrecognition of catatonia in older patients is also frequent, and research in this population is scarce. AIM To conduct a systematic review of the literature on catatonia in older people to ascertain its clinical characteristics across settings. METHODS Following the PRISMA guidelines, MEDLINE, EMBASE, and PsycINFO databases were searched from inception to December 2021, with a strategy aimed at identifying all articles published on catatonia in older adults. Titles and abstracts were scanned and selected independently by two authors. Papers investigating issues related to catatonia and/or catatonic symptoms in older people, with English abstracts available, were included. References of selected articles were revised to identify other relevant studies. RESULTS In total, 1355 articles were retrieved. After removing duplicates, 879 remained. Of the 879 identified abstracts, 669 were excluded because they did not meet the inclusion criteria. A total of 210 articles underwent full text review, and 51 were eliminated for various reasons. Fourteen more articles were selected from the references. Overall, 173 articles were reviewed: 108 case reports, 35 case series, 11 prospective cohort studies, 6 case-control studies, 3 retrospective cohort studies and 10 reviews. We found several particular aspects of catatonia in this population. Catatonia in older patients is highly prevalent and tends to have a multifactorial etiology. Older patients, compared to younger patients, have a higher risk of developing catatonia with benzodiazepine (BZD) withdrawal, in bipolar disorder, and in the general hospital. Age, together with other risk factors, was significantly associated with the incidence of deep venous thrombosis, neuroleptic malignant syndrome poor outcome, other complications and mortality. Treatment with BZDs and electroconvulsive therapy is safe and effective. Prompt treatment of its cause is essential to ensure a good prognosis. CONCLUSION Catatonia in older patients is highly prevalent and tends to have a multifactorial etiology. The risk of developing catatonia in some settings and conditions, as well as of developing complications, is high in this population. Symptomatic treatment is safe and effective, and timely etiologic treatment is fundamental.

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Section: Resultsmentioning

confidence: 99%

Catatonia in older adults: A systematic review

Jaimes-Albornoz¹,

Pellon-Santamaria²,

Nizama-Vía³

et al. 2022

WJP

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“…Neuroleptic malignant syndrome is also triggered by abrupt withdrawal of medication affecting the central nervous system. Abrupt withdrawal of levodopa in patients with Parkinson's disease is a classic example, 9 but withdrawal NMS is not confined to dopaminergic agents, as abrupt cessation of sertraline and clozapine is also reported to be associated with NMS 10,11 . However, no case of NMS associated with withdrawal of lithium has been reported to date.…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4][5][6][7][8] Neuroleptic malignant syndrome is also triggered by abrupt withdrawal of certain types of medication including dopaminergic agents, antipsychotics, and antidepressants. [9][10][11] However, no case of lithium withdrawal-associated NMS is reported.…”

Section: Neuroleptic Malignant Syndrome After Lithium Withdrawalmentioning

confidence: 99%

Neuroleptic Malignant Syndrome After Lithium Withdrawal

Okubo,

Bannai,

Seki

et al. 2023

J Clin Psychopharmacol

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“…Several cases of withdrawal catatonia after clozapine discontinuation have been described in the literature ( 36 ). In one case the catatonic symptoms were associated with a substantial CK elevation (up to 2400 U/L) ( 37 ).…”

Section: Case Presentationmentioning

confidence: 99%

Recurrent high creatine kinase levels under clozapine treatment - a case report assessing a suspected adverse drug reaction

Wiss,

Allemann,

Meyer zu Schwabedissen

et al. 2024

Front. Psychiatry

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Suspected adverse drug reactions (ADRs) during treatment with clozapine often prompt therapeutic drug monitoring (TDM) in clinical practice. Currently, there is no official recommendation for pharmacogenetic (PGx) testing in the context of clozapine therapy. In this case report, we demonstrate and discuss the challenges of interpreting PGx and TDM results highlighting the possibilities and limitations of both analytical methods. A 36-year-old male patient with catatonic schizophrenia was treated with clozapine. He experienced multiple hospitalizations due to elevated creatine kinase (CK) levels (up to 9000 U/L, reference range: 30-200 U/L). With no other medical explanation found, physicians suspected clozapine-induced ADRs. However, plasma levels of clozapine were consistently low or subtherapeutic upon admission, prompting us to conduct a PGx analysis and retrospectively review the patient’s TDM data, progress notes, and discharge reports. We investigated two possible hypotheses to explain the symptoms despite low clozapine plasma levels: Hypothesis i. suggested the formation and accumulation of a reactive intermediate metabolite due to increased activity in cytochrome P450 3A5 and reduced activity in glutathione S-transferases 1, leading to myotoxicity. Hypothesis ii. proposed under-treatment with clozapine, resulting in ineffective clozapine levels, leading to a rebound effect with increased catatonic symptoms and CK levels. After considering both data sources (PGx and TDM), hypothesis ii. appeared more plausible. By comprehensively assessing all available TDM measurements and examining them in temporal correlation with the drug dose and clinical symptoms, we observed that CK levels normalized when clozapine plasma levels were raised to the therapeutic range. This was achieved through hospitalization and closely monitored clozapine intake. Therefore, we concluded that the symptoms were not an ADR due to altered clozapine metabolism but rather the result of under-treatment. Interpreting TDM and PGx results requires caution. Relying solely on isolated PGx or single TDM values can result in misinterpretation of drug reactions. We recommend considering the comprehensive patient history, including treatment, dosages, laboratory values, clinic visits, and medication adherence.

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Clozapine Withdrawal-Induced Malignant Catatonia or Neuroleptic Malignant Syndrome: A Case Report and a Brief Review of the Literature

Cited by 15 publications

References 55 publications

Catatonia in older adults: A systematic review

Catatonia in older adults: A systematic review

Neuroleptic Malignant Syndrome After Lithium Withdrawal

Recurrent high creatine kinase levels under clozapine treatment - a case report assessing a suspected adverse drug reaction

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